This table lets you know if the ClinVar variant is observed in dbGaP data. It provides both the count of submissions to
dbGaP with the variant and the frequency of the variant in the database, not in the population. It reports two measures: called variants when the variant is observed
in the set formally submitted with a dbGaP study, and potential variants when NCBI found the variant in aligned NGS
with the dbGaP study, but we can take reads that were submitted with the study, align them to the genome, and see if that variant is observed in the reads.

Formally, called variants are submitted to dbGaP as subject genotypes and counted when a sample (subject genotype from VCF file) has at least one allele present;
potential variants are computed by examination of any aligned next generation sequence for the sample that covers the position. A sample (SRA run accession) is
counted when the allele is observed in at least 30% of the reads covering the position, and 10 or more clean reads (not flagged as artifact or PCR duplicate) cover the position.

Germline

The S121G variant in the DKC1 gene has been reported in two brothers with a diagnosis of Hoyeraal-Hreidarsson syndrome (Knight et al., 2009; Aalfs et al., 1995). The S121G variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S121G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position within the protein's catalytic domain that is conserved across species (Vuilliamy et al., 2008). In silico analysis predicts this variant is probably damaging to the protein structure/function. The S121G variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.